The symptoms and signs of hypercalcemia are now more often mild and general rather than severe renal and bone problems seen years ago:
GENERAL -symptoms such as malaise and depression
RENAL- renal colic from stones, polyuria/ nocturia, haematuria and hypertension.
BONES-bone pain.
ABDOMINAL-abdominal pain due to peptic ulceration.
In malignant diseases, hypercalcemia results from bony metastasis which indicates the malignant disease is of longstanding duration. Severe hypercalcemia is usually associated with malignant disease, hyperparathyroidism, renal dialysis or vitamin D therapy.
Corneal calcification is a marker of longstanding hypercalcemia. In primary hyperparathyroidism, only 5-10% have definite bony lesions and 20-40% renal involvement.
In longstanding cases of hypercalcemia, calcium starts getting deposited in soft tissues or can lead to renal stone formation.

Diagnosing the cause of hypercalcemia requires a complete physical history and examination which is a more complex process. [9]
Several fasting serum calcium and phosphate samples should be taken. Hypophosphataemia is common in primary hyperparathyroidism. If calcium levels are mildly elevated since long, malignancy is not likely to be the cause. Sudden onsets of elevated levels of calcium are suspected for malignancies. Most likely malignancies could be breast, lung, kidney multiple myeloma, lymphoma or leukaemias. Serum PTH levels should be measured; if high during hypercalcemia it definitely implies hyperparathyroidism.

Abdominal X-Rays show renal calculi or nephrocalcinosis. Renal function must be measured. Chest X-Ray should be done to rule out chest malignancies or sarcoidosis. Biopsy may also be done for sarcoidosis. Proteins electrophoresis should be done to confirm for myeloma. Serum TSH, T3 are necessary to diagnose underlying thyrotoxicosis. PTH reduces renal tubular reabsorption of bicarbonate, thus bicarbonate levels fall and plasma chloride levels rise in primary hyperparathyroidism.
If hyperparathyroidism is confirmed, the following tests may be useful in localization although adenomas are usually small-
Ultrasound for tumors
CT or MRI scans for better viewing and resolution.
Barium swallow may show indention of esophagus by adenoma.

The main aim of treatment is first to bring down the levels of calcium followed by treating the underlying medical condition responsible for hypercalcemia. [10]
Hydration is very important as dehydration due to vomiting or renal impairment result in concentrated urine. An increased uptake of salt can help in increased excretion of sodium following increased potassium excretion. A loop diuretic can be give to sustain salt and water replacement preventing fluid overload. In addition loop diuretics also have inhibitory action on the calcium renal resorption. Thus, this helps, to further lower the calcium levels. With this treatment calcium levels can be bought down by 1-3 mg/dl within 24 hours. Caution should be taken to prevent magnesium or potassium depletion.

Second line of treatment includes biphosphonates [11] and calcitonin therapy. Bisphosphonates are taken by osteoclasts and prevent bone resorption. Bisphosphonates are contraindicated in renal failure patients. Calcitonin also prevents bone resorption and increases urinary excretion of calcium.

All cancer patients should receive bisphosphonates as the first line of treatment may not be possible to complete without any risks and side effects. Recurrence of hypercalcemia in such patients is inevitable.
Other therapies include use of glucocorticoids. Dialysis may be opted for in severe cases with renal failure. Supplementary phosphate therapy is recommended in case of low phosphate levels.

Indications for surgery in hyperparathyroidism remain controversial, but if needed should be done by a qualified surgeon. All agree that with renal disease or bone involvement, since there is no long term treatment requires surgery. Main complication of surgery is hypocalcaemia which should be carefully monitored.

The outlook of hypercalcemia mainly depends on the cause. Mild cases of hyperparathyroidism or hypercalcemia with a treatable cause have a good prognosis. Most cases have no complications at all.
Malignancies or granulomatous diseases associated with hypercalcemia usually do not do well, which is majorly due the underlying disease rather than hypercalcemia. The usual 30 day survival in malignancies is about 50%. Many cases of malignancies [8] in final stage show hospitalization due to an emergency. Thus mortality and morbidity mainly depend on the cause and are basically a reflection of how well the disease is treated or under control.

Major causes are primary hyperparathyroidism and malignancies. Hyperparathyroidism is the commonest cause. Other causes of hypercalcemia can be listed as follows

1. BONY RESORPTIVE HYPERCALCEMIA

• Excess PTH- primary hyperparathyroidism [3]. Primary hyperparathyroidism is very frequent in women above the age of 50. Primary hyperparathyroidism can occur when all the four parathyroid glands produce too much of PTH or one single gland starts producing an excess of PTH mainly due to an adenoidal tumor. Most of these are benign growths.
• Malignancies- over 20% cases with malignancies will develop hypercalcemia at some point in their disease condition. Secondary deposits of cancers of lung or the breast are also common causes. Production of osteoclastic factors by tumors as in case of multiple myeloma is another common cause.[4]
• Endocrine diseases- Thyrotoxicosis and Addision's disease
• Immobility over a long period of time 

2. GASTROINTESTINAL ABSORPTIVE HYPERCALCEMIA

• "Milk alkali” syndrome- an increase in calcium intake
• Sarcoidosis/ Paget's disease/ Tuberculosis
• Excess of vitamin D - iatrogenic or self administered.

3. RENAL RESORPTIVE HYPERCALCEMIA

• Medications - such as thiazides or lithium pills
• Familial hypocalciuric hypercalcemia
• Kidney failure

Hypercalcemia is a common clinical occurrence which has a long duration and is mostly mild. Postmenopausal women above the age of 50 are at a higher risk, as primary hyperparathyroidism is the most common etiological factor. [5]
It occurs in 1 in 1000 population, mainly affecting elderly females. Many a times, most cases go unnoticed. Hypercalcemia tends to occur with advancing age, where hyperparathyroidism and malignancy are the main reasons.
In cases of malignancy, hypercalcemia is frequently encountered as an endocrine electrolyte disorder in hospitalized patients. The occurrence in children is unknown and rare; it is also thought to be a rare occurrence in young adults.

The human skeleton stores 98% of total body calcium while the remaining 2% circulates through the body. Out of this 2%, half is bound to proteins such as albumin and globulin and the remaining is present in the free ionized form which has the physiological effects. Thus, measuring the free calcium level is more accurate. The level of circulating protein, mainly albumin, should also be taken into account for a correct measurement. The ionized calcium or the unbound calcium is physiologically important as it takes active part in cellular activities and neuromuscular functions. [6]
Corrected [CA] =Total [CA] + (0.8 x [4.5-albumin level])
An increase in bone resorption, increased gastrointestinal absorption or a reduced excretion of calcium by kidneys can cause hypercalcemia. Total serum calcium levels between 10.5 and 12 mg per dL are considered mild while levels above 14 mg per dL can be fatal and serious.
Generally when calcium levels fall, PTH [7] a hormone secreted by parathyroid glands increases calcium levels by stimulating bone resorption and accelerating tubular resorption of calcium. Calcitrol levels also increase thereby increasing calcium levels. As PTH increases calcium, it simultaneously causes an increased excretion of phosphate by the kidneys. Thus patients show low serum phosphate levels along with hypercalcemia. Along with this PTH also causes an increase in 1, 25 dihydroxy vitamin D synthesis further aggravating hypercalcemic state.
Calcium absorption from the gut is usually reduced. Impairment of glomerular filtration can also cause hypercalcemia.

The pathophysiology is varied and can be classified as three separate syndromes-

1.  the hypercalcemia of malignancy caused by systemic mediators
2. the hypercalcemia along with localized osteoclastic disease
3. the hypercalcemia associated with myeloma.

Increased bone resorption is the characteristic feature in all the three syndromes. In malignancies, tumor cells as well host cells stimulate humoral mediators which cause an enhanced activity of osteoclasts. This leads to hypercalcemia when the rate of entry of calcium in the blood increases in comparison to its removal from blood. Therefore when GI and osteoclastic bone absorption increases the levels of calcium, beyond the capacity of kidneys to eliminate it, that is when calcium enters the extra cellular fluid compartment and renal excretion or bone mineralization get impaired. Hypercalcemia is always preceded by hypercalciuria. When the kidney is unable to excrete the excess calcium, the patient develops hypercalcemia. A hypercalcemia state interferes with the action of ADH hormone on the distal tubule causing a state of nephrogenic diabetes insipidus resulting in polyuria. With the nausea and vomiting, thirst mechanism may not be active thus dehydration may occur.

There is no prevention for hypercalcemia other than early detection and treatment. An accurate diagnosis of the underlying cause will help to stabilize calcium levels faster. Any known history of hypercalcemia or hyperparathyroidism in the family should be mentioned to the physician for early screening and detection. Women above 50 should regularly check calcium levels if they show symptoms of hypercalcemia. Vitamin D and calcium supplements should be taken only under the guidance of a physician.

Hypercalcemia is a clinical condition characterized by elevated levels of calcium in the blood. It is much more common than hypocalcaemia and is frequently detected incidentally with multichannel chemical analyzers. The normal range of calcium is 9-10.5 mg/dl or 2.2-2.6mmol/L. Mild asymptotic hypercalcemia is mainly a laboratory finding and usually suggestive of some other disease which needs a careful work up and treatment. [1]
Calcium is a vital mineral of the body required for optimal functioning of the bones, muscles and nerves. The main regulators of calcium in the body are PTH, Vitamin D and calcitonin. Parathyroid hormone is released by parathyroid glands [2] which is the chief regulator of calcium in the body. Calcitonin is produced by specialized cells of the thyroid gland. Together these three hormones act on the kidneys, bones and GI tract to maintain levels of calcium in the blood stream. The simplest way to remember the presentation of hypercalcemia is by the phrase "moans, stones, groans and bones”. The intensity, duration and severity of this condition vary. The most common cause of hypercalcemia is hyperparathyroidism. Most cases of malignancies have hypercalcemia as an associated condition. Onset of hypercalcemia usually indicates a poor outlook for malignancies.
The options of treatment depend upon the severity and cause of hypercalcemia. Both medical and surgical modes of treatment are available. The outlook of this condition majorly depends upon the causation.

Hypercalcemia is a clinical condition where there are increased calcium levels in the blood. The normal levels of calcium in the body are 9-10.5mg/dL. Most times mild cases of hypercalcemia are not detected and go unnoticed. Calcium is an important mineral required by the body for smooth functioning of the bones, muscle, nerves and brain. Calcium is maintained in the body by three hormones which are PTH, Vitamin D and calcitonin. Any irregularity in these three causes calcium levels to fall or rise. The most common cause is the over activity of parathyroid glands which are four small glands situated near the thyroid gland which cause increase in PTH levels which thereby causes increased calcium levels. No obvious symptoms are seen, but slowly it can lead to major clinical conditions like tiredness, bony pains, alterations in blood pressure and bowel function. It is more common in menopausal women. A simple blood test can check blood calcium levels. A PTH level can also be checked for. Some scans maybe required incase of cancers or tumors. A consultation with your physician will help you control calcium levels. Treatment mainly involves lowering levels of calcium along with adequate hydration. Calcium and vitamin D supplements should always be taken under medical guidance.

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